Jaap Keijer
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View article: Assessing the involvement of tumor-secreted factors in the inhibition of muscle differentiation
Assessing the involvement of tumor-secreted factors in the inhibition of muscle differentiation Open
View article: Primary‐Stage Colon Cancer Impairs Muscle Energy Metabolism by Suppressing Mitochondrial Complex I Activity
Primary‐Stage Colon Cancer Impairs Muscle Energy Metabolism by Suppressing Mitochondrial Complex I Activity Open
Background Colon cancer (CC), the third most common cancer worldwide, is accompanied by cachexia in 30% of patients. Its associated muscle loss directly impairs therapeutic response and survival. Early intervention is crucial, yet the unde…
View article: Anabolic Effects of Salbutamol Are Lost Upon Immobilization
Anabolic Effects of Salbutamol Are Lost Upon Immobilization Open
Background Periods of muscle disuse occur during hospitalization, illness or the recovery from (sports) injury and lead to a rapid loss of muscle mass and the development of insulin resistance. Salbutamol is a fast‐acting β2‐adrenoreceptor…
View article: Nicotinamide nucleotide transhydrogenase dysfunction transcriptionally impacts mitochondrial β-oxidation and neuromuscular junction in M. Gastrocnemius of 24-day-old mice
Nicotinamide nucleotide transhydrogenase dysfunction transcriptionally impacts mitochondrial β-oxidation and neuromuscular junction in M. Gastrocnemius of 24-day-old mice Open
Nicotinamide nucleotide transhydrogenase (NNT) is a key mitochondrial enzyme generating NADPH by utilizing the proton gradient produced by oxidative phosphorylation (OXPHOS), thereby linking redox homeostasis to mitochondrial energy metabo…
View article: Increased ambient temperature mitigates pathology in the <i>Ndufs4</i> <sup>-/-</sup> mouse model of pediatric Leigh Syndrome
Increased ambient temperature mitigates pathology in the <i>Ndufs4</i> <sup>-/-</sup> mouse model of pediatric Leigh Syndrome Open
Leigh syndrome (LS) is a devastating mitochondrial disease (MD) for which there is no treatment. Together with Leigh-like syndrome (LLS), LS constitutes part of the Leigh syndrome spectrum (LSS) disorders, which are the most frequent manif…
View article: Dual effects of nicotinamide on aging-related arrhythmia: protective at low dose, proarrhythmic at high doses
Dual effects of nicotinamide on aging-related arrhythmia: protective at low dose, proarrhythmic at high doses Open
Background Cardiac arrhythmia and dysfunction progressively increase with age, both of which are closely associated with a decline in NAD + . Supplementation with nicotinamide (NAM), a critical NAD + precursor, has shown protection in expe…
View article: A robust method for assessing mitochondrial function in healthy and diseased frozen cardiac tissue
A robust method for assessing mitochondrial function in healthy and diseased frozen cardiac tissue Open
Cardiovascular diseases are often associated with impairment in mitochondrial function. However, existing respirometry measuring mitochondrial function are limited by the necessity of fresh tissue samples. This study develops a method with…
View article: Resveratrol Prevents Weight Gain, Counteracts Visceral Adipose Tissue Dysfunction, and Improves Hypothalamic Leptin Sensitivity in Diet‐Induced Obese Rats
Resveratrol Prevents Weight Gain, Counteracts Visceral Adipose Tissue Dysfunction, and Improves Hypothalamic Leptin Sensitivity in Diet‐Induced Obese Rats Open
In obesity, increased adipocyte size is associated with metabolic complications, while elevated adipocyte numbers are considered a protective mechanism against metabolic disturbances. Adipose tissue dysfunction leads to decreased leptin se…
View article: Six-hour hypoxia-induced protein degradation in M. gastrocnemius of 24-day-old mice by activating FOXO1 and suppressing AKT-mTORC1
Six-hour hypoxia-induced protein degradation in M. gastrocnemius of 24-day-old mice by activating FOXO1 and suppressing AKT-mTORC1 Open
We newly investigated an acute (6 h) hypoxic exposure (12% O 2 ) in developing and growing M. gastrocnemius of 24-day-old mice. This acute hypoxia significantly enhanced muscle protein breakdown via the activation of FOXO1 and subsequently…
View article: Quantitative interpretation and modeling of continuous nonprotein respiratory quotients
Quantitative interpretation and modeling of continuous nonprotein respiratory quotients Open
With the here proposed mathematical model, we provide a new tool to convert continuous RER data into more accurate estimations of %G ox and %L ox . It circumvents the use of nonprotein respiratory quotient tables and thereby aids and simpl…
View article: Mix it up: Stability of oil-in-water emulsions made with commercial pea and potato protein isolate as emulsifier
Mix it up: Stability of oil-in-water emulsions made with commercial pea and potato protein isolate as emulsifier Open
View article: A novel and robust method for assessing mitochondrial (dys)function in healthy and diseased frozen cardiac tissue
A novel and robust method for assessing mitochondrial (dys)function in healthy and diseased frozen cardiac tissue Open
Cardiovascular diseases are often associated with impairment in mitochondrial function detected by reduced mitochondrial oxygen consumption using high-resolution respirometry. However, existing respirometry protocols are limited by the nec…
View article: Blood-based biomarkers for early frailty are sex-specific: validation of a combined in silico prediction and data-driven approach
Blood-based biomarkers for early frailty are sex-specific: validation of a combined in silico prediction and data-driven approach Open
Frailty is characterized by loss of physical function and is preferably diagnosed at an early stage (e.g., during pre-frailty). Unfortunately, sensitive tools that can aid early detection are lacking. Blood-based biomarkers, reflecting pat…
View article: Diabetic Glycation of Human Serum Albumin Affects Its Immunogenicity
Diabetic Glycation of Human Serum Albumin Affects Its Immunogenicity Open
Advanced glycation end-products (AGEs) are products of a non-enzymatic reaction between amino acids and reducing sugars. Glycated human serum albumin (HSA) increases in diabetics as a consequence of elevated blood glucose levels and glycat…
View article: Lactation affects postweaning metabolic profiles, but not follicle size in multiparous sows
Lactation affects postweaning metabolic profiles, but not follicle size in multiparous sows Open
Young sows mobilise body reserves to support milk production during lactation, resulting in a negative energy balance (NEB). This NEB affects the development of follicles and oocytes that give rise to the next litter. Decreased IGF1 levels…
View article: TLCD4 as Potential Transcriptomic Biomarker of Cold Exposure
TLCD4 as Potential Transcriptomic Biomarker of Cold Exposure Open
(1) Background: Cold exposure induces metabolic adaptations that can promote health benefits, including increased energy disposal due to lipid mobilization in adipose tissue (AT). This study aims to identify easily measurable biomarkers mi…
View article: Human SIRT5 variants with reduced stability and activity do not cause neuropathology in mice
Human SIRT5 variants with reduced stability and activity do not cause neuropathology in mice Open
View article: Translatability of mouse muscle-aging for humans: the role of sex
Translatability of mouse muscle-aging for humans: the role of sex Open
View article: Performance of TMRM and Mitotrackers in mitochondrial morphofunctional analysis of primary human skin fibroblasts
Performance of TMRM and Mitotrackers in mitochondrial morphofunctional analysis of primary human skin fibroblasts Open
Mitochondrial membrane potential (Δψ) and morphology are considered key readouts of mitochondrial functional state. This morphofunction can be studied using fluorescent dyes ("probes") like tetramethylrhodamine methyl ester (TMRM) and Mito…
View article: <i>SIRT5</i>variants from patients with mitochondrial disease are associated with reduced SIRT5 stability and activity, but not with neuropathology
<i>SIRT5</i>variants from patients with mitochondrial disease are associated with reduced SIRT5 stability and activity, but not with neuropathology Open
Summary SIRT5 is a sirtuin deacylase that represents the major activity responsible for removal of negatively-charged lysine modifications, in the mitochondrial matrix and elsewhere in the cell. In benign cells and mouse models, under basa…
View article: Dietary Galactose Increases the Expression of Mitochondrial OXPHOS Genes and Modulates the Carbohydrate Oxidation Pathways in Mouse Intestinal Mucosa
Dietary Galactose Increases the Expression of Mitochondrial OXPHOS Genes and Modulates the Carbohydrate Oxidation Pathways in Mouse Intestinal Mucosa Open
View article: Functional and molecular profiling of fasted piglets reveals decreased energy metabolic function and cell proliferation in the small intestine
Functional and molecular profiling of fasted piglets reveals decreased energy metabolic function and cell proliferation in the small intestine Open
Fasting is identified as one of the underlying causes potentiating diarrhea development, both in piglets and humans. With this study, we demonstrate that fasting decreases the metabolism of intestinal epithelial cells, on a functional and …
View article: Study protocol: Identification and validation of integrative biomarkers of physical activity level and health in children and adolescents (INTEGRActiv)
Study protocol: Identification and validation of integrative biomarkers of physical activity level and health in children and adolescents (INTEGRActiv) Open
Background Physical activity (PA) provides health benefits across the lifespan and improves many established cardiovascular risk factors that have a significant impact on overall mortality. However, discrepancies between self-reported and …
View article: Normobaric hypoxia shows enhanced FOXO1 signaling in obese mouse gastrocnemius muscle linked to metabolism and muscle structure and neuromuscular innervation
Normobaric hypoxia shows enhanced FOXO1 signaling in obese mouse gastrocnemius muscle linked to metabolism and muscle structure and neuromuscular innervation Open
Skeletal muscle relies on mitochondria for sustainable ATP production, which may be impacted by reduced oxygen availability (hypoxia). Compared with long-term hypoxia, the mechanistic in vivo response to acute hypoxia remains elusive. Ther…
View article: Evidence for sex-specific intramuscular changes associated to physical weakness in adults older than 75 years
Evidence for sex-specific intramuscular changes associated to physical weakness in adults older than 75 years Open
View article: Omics biomarkers and an approach for their practical implementation to delineate health status for personalized nutrition strategies
Omics biomarkers and an approach for their practical implementation to delineate health status for personalized nutrition strategies Open
Personalized nutrition (PN) has gained much attention as a tool for empowerment of consumers to promote changes in dietary behavior, optimizing health status and preventing diet related diseases. Generalized implementation of PN faces diff…
View article: Translational characterization of the temporal dynamics of metabolic dysfunctions in liver, adipose tissue and the gut during diet-induced NASH development in Ldlr−/−.Leiden mice
Translational characterization of the temporal dynamics of metabolic dysfunctions in liver, adipose tissue and the gut during diet-induced NASH development in Ldlr−/−.Leiden mice Open
View article: Sex differences in skeletal muscle-aging trajectory: same processes, but with a different ranking
Sex differences in skeletal muscle-aging trajectory: same processes, but with a different ranking Open
Sex differences in muscle aging are poorly understood, but could be crucial for the optimization of sarcopenia-related interventions. To gain insight into potential sex differences in muscle aging, we recruited young (23 ± 2 years, 13 male…
View article: Single and Joined Behaviour of Circulating Biomarkers and Metabolic Parameters in High-Fit and Low-Fit Healthy Females
Single and Joined Behaviour of Circulating Biomarkers and Metabolic Parameters in High-Fit and Low-Fit Healthy Females Open
Biomarkers are important in the assessment of health and disease, but are poorly studied in still healthy individuals with a (potential) different risk for metabolic disease. This study investigated, first, how single biomarkers and metabo…
View article: Caloric Restriction Combined with Immobilization as Translational Model for Sarcopenia Expressing Key-Pathways of Human Pathology
Caloric Restriction Combined with Immobilization as Translational Model for Sarcopenia Expressing Key-Pathways of Human Pathology Open
The prevalence of sarcopenia is increasing while it is often challenging, expensive and time-consuming to test the effectiveness of interventions against sarcopenia. Translational mouse models that adequately mimic underlying physiological…